Mitsuhiko Nose

Effect of Hachimi-jio-gan on scopolamine-induced memory impairment and on acetylcholine content in rat brain

The effect of Hachimi-jio-gan (HJ) on scopolamine induced memory impairment was studied using a radial maze performance, the effect of HJ on the central cholinergic system as measured by acetylcholine (ACh) content, choline acetyltransferase (CAT) and acetylcholinesterase (AChE) activities was also examined. HJ (0.01-1.0 g/kg, p.o.) showed no influence on the radial maze performance. However, with the administration of scopolamine (0.5 mg/kg, i.p.), the number of the correct choices decreased and the number of the error choices increased. HJ (0.1 and 0.5 g/kg, p.o.) reduced this scopolamine-induced cognitive disturbance. The effect of HJ on ACh content and enzyme activities in the brain, frontal cortex, hippocampus and striatum was also investigated. In normal rats, HJ (0.1 and 0.5 g/kg, p.o. x 7 days) significantly increased ACh content in the frontal cortex, although it did not increased ACh content in the hippocampus. In scopolamine-treated rats, ACh content decreased in the brain regions examined. HJ (0.5 g/kg, p.o.) inhibited a decrease in ACh content in the frontal cortex, and with the same dosage of HJ increased CAT activity in the frontal cortex and AChE activity in the hippocampus. These results suggest that the behavioral effects of HJ may be related to its effect on the central cholinergic system.

Dermal mast cells play a central role in the incidence of scratching behavior in mice induced by multiple application of the hapten, 2,4,6‐trinitrochlorobenzene

Abstract:  Repeated application of 1% 2,4,6‐trinitrochlorobenzene (TNCB) in acetone solution causes chronic skin inflammation in BALB/c mice. Associated scratching behavior gradually appeared, and chronic scratching behavior was established over 40 days after the initial application of TNCB. In order to explore the possible involvement of T cells and mast cells in the appearance of pruritus, we examined the response of athymic nude mice and genetically mast‐cell‐deficient mice. We could not detect either severe skin inflammation or immunoglobulin (Ig)E production in T‐cell‐deficient BALB/c nu/nu mice even after 80 days of TNCB treatment, whereas typical severe skin inflammation and IgE production were observed in mast‐cell‐deficient WBB6F1‐W/Wv and WBB6F1‐Sl/Sld mice. Furthermore, we observed persistent scratching behavior in WBB6F1‐W/Wv mice, but not in BALB/c nu/nu and WBB6F1‐Sl/Sld mice. Histological examination of TNCB‐treated animals revealed the development of dermal mast cells in W/Wv mice but not in Sl/Sld mice. Degranulation of dermal mast cells was observed in the WBB6F1‐W/Wv genotype, but most mast cells remained intact in TNCB‐treated BALB/c nu/nu mice. These results suggest that mast cells play a pivotal role in the incidence of scratching behavior in this chronic pruritus model.

The Herbal Medicine Compound Falcarindiol from Notopterygii Rhizoma Suppresses Dendritic Cell Maturation

Dendritic cells (DCs) are important for regulating the immune response. We report an herbal medicine compound called falcarindiol that affects DC function. Ethanol extracts of 99 crude drugs that are the main components of 210 traditional Japanese medicines (Kampo medicine) approved by the Ministry of Health, Labor and Welfare in Japan were prepared and screened using the murine epidermal-derived Langerhans cell line XS106. Notopterygii Rhizoma strongly suppressed major histocompatibility complex (MHC) class II expression in XS106 cells. Activity-guided fractionation led to the isolation and identification of falcarindiol as a principal active compound in Notopterygii Rhizoma. Falcarindiol (1–5 μM) dose-dependently suppressed MHC II expression in XS106 cells. Fresh-isolated bone marrow-derived DCs were examined for the production of MHC II, CD80, CD86, interleukin (IL)-12p70, and IL-10. Treatment of bone marrow-derived DCs with 5 μM falcarindiol significantly inhibited lipopolysaccharide-induced phenotype activation and cytokine secretion and inhibited MHC II expression by CD40 ligation, but not phorbol 12-myristate 13-acetate + ionomycin or IL-12. Falcarindiol inhibited DC maturation by blocking the canonical pathway of nuclear factor-κB and phosphorylated p38. Topical application of 0.002 and 0.01% falcarindiol before sensitization dose-dependently suppressed delayed-type hypersensitivity to ovalbumin (p < 0.01). Falcarindiol induces immunosuppressive effects in vitro and in vivo and might be a novel therapy for autoimmune or allergic diseases.

Sho‐saiko‐to and Saiko‐keisi‐to, the traditional Chinese and Japanese herbal medicines, altered hepatic drug‐metabolizing enzymes in mice and rats when administered orally for a long time

As the consumption of herbal remedies has increased, the opportunity that such herbal medicines are co‐administered with other drugs has also risen gradually and we are, therefore, very much concerned about herb–drug interactions. We examined the effects of pre‐administration of Kampo medicines (Sho‐saiko‐to, Saiko‐keishi‐to, Shigyaku‐san and Dai‐saiko‐to) on the pentobarbital‐induced sleeping time in mice and rats, to clarify the possibility that they could affect the drug‐metabolizing enzymes. The administration of Sho‐saiko‐to and Saiko‐keishi‐to for 4 weeks significantly shortened the pentobarbital‐induced sleeping time in mice and the administration of Sho‐saiko‐to for 2 weeks significantly reduced the sleeping time in rats. Furthermore, we tried to identify the molecular species of rat cytochrome P450s (CYPs) affected by Sho‐saiko‐to and Saiko‐keishi‐to by competitive RT‐PCR. The oral administration of Sho‐saiko‐to for 2 weeks up‐regulated the mRNA expression of CYP2B, CYP3A1, CYP2E1 and CYP4A1 in rats. The treatment with Saiko‐keishi‐to for 2 weeks also up‐regulated the mRNA expression of CYP2B, CYP3A1 and CYP4A1. Sho‐saiko‐to and Saiko‐keishi‐to may potentially influence the drug‐metabolizing enzymes in man, and would thus require much attention when used in the clinical situation.

The role of IgE and repeated challenge in the induction of persistent increases in scratching behavior in a mouse model of allergic dermatitis

Previously, we indicated that athymic BALB/c-nu/nu (nude) mice that had been repeatedly treated with 2,4,6-trinitrochlorobenzene (TNCB) failed to exhibit chronic scratching behavior in spite of the accumulation of dermal mast cells in the lesion. The mice also failed to produce specific IgE or potent dermatitis. In the present study, therefore, we aimed to examine the role of IgE and repeated hapten treatment in the induction of scratching behavior and dermatitis using nude mice and trinitrophenol (TNP)-specific IgE-transgenic mice. The ears of nude mice were treated with TNCB 6 times at intervals of 48 h, and TNP-specific IgE was administered to the mice intravenously before the sixth TNCB treatment. The nude mice that had been supplemented with IgE exhibited a persistent increase in scratching behavior and continuous degranulation of mast cells. Furthermore, a potent immediate ear swelling was induced, although no biphasic dermatitis pattern was observed. On the other hand, the IgE-transgenic mice failed to exhibit persistent increases in scratching behavior after a single TNCB treatment, although biphasic ear swelling was observed. These results indicate that specific IgE plays an essential role in the induction of persistent increases in scratching behavior and continuous degranulation of mast cells. Furthermore, repeated challenge with the hapten also plays an important role in persistent increases in scratching behavior through accumulation and continuous activation of mast cells.

Lignans from Trachelospermum axillare

Abstract A new lignan, traxillaside and nine known lignans, arctigenin, traxillagenin, trachelogenin, matairesinol, nortrachelogenin, arctiin, tracheloside, mat

Protective effect of Hachimi-jio-gan, an oriental herbal medicinal mixture, against cerebral anoxia

The protective effect of Hachimi-jio-gan (HJ) against cerebral anoxia was investigated with various experimental models in mice. Minimal effective dose of HJ which significantly prolonged the survival time was 0.5 g/kg, p.o. for normobaric hypoxia and 0.5 g/kg, p.o. for KCN- (4 mg/kg, i.v.) induced anoxia. HJ reduced the duration of coma induced by a sublethal dose of KCN (1.8 mg/kg, i.v.) in a dose-dependent manner. Furthermore HJ potentiated the anti-anoxic effect of physostigmine and the effect of HJ was diminished by the treatment with atropine.

The role of a crude polysaccharide fraction in the macrophage activation by “Shosaikoto”

Oral administration of Shosaikoto (1.4g/kg) enhanced phagocytosis of casein-induced murine peritoneal macrophages and nitric oxide (NO) production of thioglycilate broth-induced murine peritoneal macrophages. To clarify the kind of compounds are responsible for this augmentation of macrophage function, ethanol-precipitation was carried out to produce two fractions: one of ethanol-precipitates (EP) and one ethanol-soluble (ES). The EP fraction consisted of polysaccharide and showed enhancement of phagocytosis and NO production comparable to Shosaikotos. On the other hand, the ES fraction consisted of low molecular compounds and did not affect macrophage function. These results suggest a crude polysaccharide fraction plays an important role in Shosaikotos macrophage activation.

Novel cleavage of the glycosidic bond of saponins in alcoholic alkali metal solution containing a trace of water

Treatment of saikosaponin c (8) with alcoholic alkali metal solution containing a trace of water afforded the sapogenin saikogenin E and three new partially hydrolysed prosapogenins in satisfactory yield.

The role of crude polysaccharide fractions on the mitogenic activity by Shosaikoto

Shosaikoto, which is one of the Japanese and Chinese traditional herbal medicine mixtures, has several immunomodulating activities. Especially, Shosaikoto is a potent polyclonal B cell mitogen in vivo and in vitro. In order to characterize the active substances for mitogenic activity, Shosaikoto was fractionated by means of ethanol precipitation to give two fractions, called ethanol-precipitate (EP) fraction and ethanol-soluble (ES) fraction. The EP fraction consisted mainly of polysaccharides and showed significant mitogenic activity. The ES fraction consisted of low molecular compounds and did not show the activity in vitro. The EP fraction of hot water extracts of Glycyrrhizae Radix and Bupureuri Radix showed the activities, and the ES fraction of a hot water extract of Glycyrrhizae Radix and all fractions of hot water extract of Scutellariae Radix showed the cytotoxicity. These results suggested that the crude polysaccharide fractions could play an important role in the mitogenic activity by Shosaikoto.